Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model
Breast cancer predominantly metastasizes to the skeleton. Mechanical loading is reliably anabolic in bone, and also inhibits bone metastatic tumor formation and bone loss in vivo. To study the underlying mechanisms, we developed a 3D culture model for osteocytes, the primary bone mechanosensor. We v...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402307456X |
| _version_ | 1797646624637321216 |
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| author | Blayne A. Sarazin Boyuan Liu Elaine Goldman Ashlyn N. Whitefield Maureen E. Lynch |
| author_facet | Blayne A. Sarazin Boyuan Liu Elaine Goldman Ashlyn N. Whitefield Maureen E. Lynch |
| author_sort | Blayne A. Sarazin |
| collection | DOAJ |
| description | Breast cancer predominantly metastasizes to the skeleton. Mechanical loading is reliably anabolic in bone, and also inhibits bone metastatic tumor formation and bone loss in vivo. To study the underlying mechanisms, we developed a 3D culture model for osteocytes, the primary bone mechanosensor. We verified that MLO-Y4s responded to perfusion by reducing their rankl and rankl:opg gene expression. We next cultured MLO-Y4s with tumor-conditioned media (TCM) collected from human breast cancer cells (MDA-MB-231s) and a corresponding bone-homing subclone to test the impacts on osteocytes’ mechanosensation. We found that TCM from the bone-homing subclone was more detrimental to MLO-Y4 growth and viability, and it abrogated loading-induced changes to rankl:opg. Our studies demonstrate that MLO-Y4s, including their mechanoresponse to perfusion, were more negatively impacted by soluble factors from bone-homing breast cancer cells compared to those from parental cells. |
| first_indexed | 2024-03-11T15:04:21Z |
| format | Article |
| id | doaj.art-f6816697a04e4d2abb333df5d9666feb |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T15:04:21Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f6816697a04e4d2abb333df5d9666feb2023-10-30T06:05:32ZengElsevierHeliyon2405-84402023-10-01910e20248Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading modelBlayne A. Sarazin0Boyuan Liu1Elaine Goldman2Ashlyn N. Whitefield3Maureen E. Lynch4Department of Mechanical Engineering, University of Colorado, Boulder, CO, 80309, USADepartment of Mechanical Engineering, University of Colorado, Boulder, CO, 80309, USADepartment of Mechanical Engineering, University of Colorado, Boulder, CO, 80309, USADepartment of Mechanical Engineering, University of Colorado, Boulder, CO, 80309, USADepartment of Mechanical Engineering, University of Colorado, Boulder, CO, 80309, USA; BioFrontiers Institute, University of Colorado, Boulder, CO, 80309, USA; Corresponding author. Department of Mechanical Engineering University of Colorado 427 UCB, Boulder, CO, 80309, USA.Breast cancer predominantly metastasizes to the skeleton. Mechanical loading is reliably anabolic in bone, and also inhibits bone metastatic tumor formation and bone loss in vivo. To study the underlying mechanisms, we developed a 3D culture model for osteocytes, the primary bone mechanosensor. We verified that MLO-Y4s responded to perfusion by reducing their rankl and rankl:opg gene expression. We next cultured MLO-Y4s with tumor-conditioned media (TCM) collected from human breast cancer cells (MDA-MB-231s) and a corresponding bone-homing subclone to test the impacts on osteocytes’ mechanosensation. We found that TCM from the bone-homing subclone was more detrimental to MLO-Y4 growth and viability, and it abrogated loading-induced changes to rankl:opg. Our studies demonstrate that MLO-Y4s, including their mechanoresponse to perfusion, were more negatively impacted by soluble factors from bone-homing breast cancer cells compared to those from parental cells.http://www.sciencedirect.com/science/article/pii/S240584402307456XBreast cancerBone metastasis3D modelsOsteocyteMechanobiology |
| spellingShingle | Blayne A. Sarazin Boyuan Liu Elaine Goldman Ashlyn N. Whitefield Maureen E. Lynch Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model Heliyon Breast cancer Bone metastasis 3D models Osteocyte Mechanobiology |
| title | Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model |
| title_full | Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model |
| title_fullStr | Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model |
| title_full_unstemmed | Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model |
| title_short | Bone-homing metastatic breast cancer cells impair osteocytes’ mechanoresponse in a 3D loading model |
| title_sort | bone homing metastatic breast cancer cells impair osteocytes mechanoresponse in a 3d loading model |
| topic | Breast cancer Bone metastasis 3D models Osteocyte Mechanobiology |
| url | http://www.sciencedirect.com/science/article/pii/S240584402307456X |
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